Parasitic diseases in animals cause substantial suffering and economic losses throughout the world. Thus, treatment of parasitic infections remains an important global endeavor. The causative organisms include helminths, such as nematodes, cestodes, and trematodes. These organisms can infect, for example, the stomach, intestinal tract, lymphatic system, muscle tissues, kidney, liver, lungs, heart, and brain of animals.
There are many known drugs (or“anthelmintic agents”) available to treat various helminith parasite infections, see, e.g., McKellar, Q. A., et al., “Veterinary anthelmintics: old and new,” Review: Trends in Parasitology, 20(10), 456-61 (October 2004). These anthelmintic agents treat specifically either nematode or trematode infections or have a broader anthelmintic spectrum. An example of an anthelmintic agent with sole effect on cestodes (tapeworms) is praziquantel. Some primary nematicidal compounds like fenbendazole, mebendazole, oxfendazole, albendazole have a broader spectrum than nematodes and treat cestode infections as well. Closantel, rafoxanide and triclabendazole are examples of specific compounds for the treatment of trematode infections (flukes).
While many parasitic infections can be treated with known drugs, evolutionary development of resistance by the parasites can render such drugs obsolete over time, see, e.g., Jabbar, A., et al., “Anthelmintic resistance: the state of play revisited,” Life Sciences, 79, 2413-31 (2006). In addition, known drugs may have other deficiencies, such as limited spectrum of activity and the need for repeated treatments.
In WO 94/29309 and WO 98/28297 spiro-substituted azacyclic compounds are disclosed which are useful as neurokinin antagonists. In WO 98/25605 and WO 99/64002 spiro-substituted azacyclic compounds are disclosed which are useful as modulators of chemokinine receptor activity and melanocortin receptor agonists respectively. In WO 03/106457, A1 spiroindoline derivatives with insecticidal properties are disclosed.
There still exists a need for new medicaments, such as antiparasitic agents to ensure safe, effective, and convenient treatment of a wide range of parasitic helminth infections over a long period of time.